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עמוד בית
Thu, 18.07.24

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December 2006
M. Tokar, D. Bobilev, S. Ariad and D.B. Geffen

Background: Disseminated intravascular coagulation associated with malignant bone marrow involvement has been described as a rare complication of gastric carcinoma and most patients die within 1–4 weeks. Effective chemotherapy of the underlying malignancy may be the only way to control acute DIC[1].

Objectives: To assess the benefit of infusional 5-fluorouracil as the primary treatment of metastatic gastric carcinoma and DIC at diagnosis.

Methods: From February 2001 to January 2005, six women (median age 48 years) with gastric carcinoma who presented with diffuse bone metastases and acute DIC were treated in our department. Diagnosis was based on primary gastric and bone marrow biopsies. DIC was confirmed by laboratory findings. Initial treatment consisted of infusional 5FU[2] 200 mg/m2/day. When the bleeding tendency stopped, cisplatin 60 mg/m2 and epirubicin 50 mg/m2 given every 3 weeks were added.

Results: Within one week of starting the treatment, the clinical and laboratory signs of acute DIC were resolved in five of six patients. Upon clinical improvement, five patients subsequently received epirubicin and cisplatin. Survival, however, was short (mean 15 weeks). All patients died with symptoms of bleeding, showing clinical and laboratory signs of DIC.

Conclusions: Based on our experience, infusional 5FU is an effective regimen with negligible myelosuppression; thus, it may be a good choice as initial therapy for this group of patients. The response induced by protracted 5FU was usually short and lasted for a few weeks only. Therefore, once DIC symptoms are controlled, the addition of newer cytotoxic drugs may be necessary to consolidate the remission.







[1] DIC = disseminated intravascular coagulation

[2] 5FU = 5-fluorouracil





 

August 2006
H. Dar, C. Zuck, S. Friedman, R. Merkshamer and R. Gonen
 Background: The decision to undergo prenatal testing is influenced by ethnic or religious factors.

Objectives: To evaluate factors that might influence the decision of pregnant women to choose chorionic villous sampling for prenatal testing.

Methods: The study group comprised 239 women referred for prenatal diagnosis who elected to undergo CVS[1]. The data were analyzed according to indication, ethnic group and religion.

Results: Among women undergoing CVS because of advanced maternal age and because of anxiety, we noted a significantly high proportion of unbalanced families, i.e., with three or more children of the same gender and deviated gender ratio. We found a significant excess of males among the Jewish families and a significant excess of females among the non-Jewish families. Jews were over-represented in the monogenic group while Christian Arabs were over-represented in the maternal age/anxiety group.

Conclusions: The proportion of women who chose CVS for prenatal diagnosis varied according to indication, ethnic group and religion. The data in this study indicate that CVS may have been utilized for balancing families with ≥ 3 or more children of the same sex. Christian Arabs chose CVS more often than the other groups. Jewish women may have utilized CVS for family balancing of both sexes, while non-Jews may have utilized CVS for balancing families with ≥ 3 daughters. 


 





[1] CVS = chorionic villous sampling


I. Hartmann, K. Weiss, T. Bistritzer, S. Baram and M. Goldman
April 2006
L. Kaplun, Y. Ivantsiv, A. Bakhrat, R. Tzirkin, K. Baranes, N. Shabek, and D. Raveh

We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs[1], and this is required for turnover of SCF Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.






[1] UIM = ubiquitin-interacting motif


March 2006
H. Schayek, M. Krupsky, P. Yaron, A. Yellin, D.A. Simansky and E. Friedman

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.






[1] NSCLC = non-small cell lung cancer

[2] DNA-MMR = DNA mismatch repair

[3] MSI = microsatellite instability

[4] LOH = loss of heterozygosity


February 2006
D. Soffer, O. Zmora, J.B. Klausner, O. Szold, A. Givon, P. Halpern, C. Schulman and K. Peleg

Background: The contribution of drugs and alcohol to current trauma‑related morbidity and mortality in Israel is not known. Identification of these factors in the fast-changing demographics of the Israeli population might lead to better care and, no less importantly, to targeted prevention measures.

Objectives: To determine the incidence of alcohol‑related trauma, and to specify the time of day, the cause of trauma, and the morbidity and mortality rates as compared to non-alcohol‑associated trauma in the tertiary trauma unit of a large medical center in Tel Aviv.

Methods: Data were obtained from the Israel National Trauma Registry, based on patient records in our institution (Tel Aviv Sourasky Medical Center) from January 2001 to December 2003.

Results: Of the 5,529 patients who were enrolled in the study, 170 had high alcohol blood levels (> 50 mg/dl). Patients intoxicated with alcohol had higher rates of road accident injuries (35% versus 24% non‑intoxicated) and stab wounds (29% vs. 7%). The Injury Severity Score of the alcohol‑intoxicated patients was higher (32% ³ 16 vs. 12% ³ 16). The alcohol‑intoxicated patients were more likely to be non-Jewish (34% vs. 9%), young (82% aged 15–44 years) and males (91%). Most of the alcohol‑related injuries occurred during the weekend (47%) and during evening‑late night hours (from 7 a.m. to 11 p.m.; 55%).

Conclusions: Alcohol‑associated trauma differs from non-alcohol‑associated trauma in many ways. Since the population at risk can be identified, it is important that legislative, social, enforcement and educational measures be adopted to reduce the extent of alcohol abuse and thereby improve the level of public safety.
 

January 2006
G. Reisler, T. Tauber, R. Afriat, O.Bortnik and M. Goldman

Background: The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions.

Objectives: To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity.

Methods: The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13–18 years) with morbid obesity (body mass index over the 95th percentile for age and/or ≥ 30 kg/m²) were treated with sibutramine 10 mg once a day for 1 year.

Results: Mean BMI[1] was 40 ± 5.6 kg/m² (range 30.1–49.5 kg/m²) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 ± 4.9 and 35.9 ± 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated.

Conclusions: Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.






[1] BMI = body mass index


December 2005
M. Rottem, A. Zitansky, Y. Horovits.

Background: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care.

Objective: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma during this period.

Methods: All records from pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions

Results: There were 1584 admissions, 1208 were first-time admissions and 374 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease of re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates.

Conclusions: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease the asthma's severity, morbidity, and resultant hospital admissions.
 

Y. Baruch, M. Kotler, J. Benatov, R. D. Strous.

Background: Analysis of the trends in psychiatric admissions and discharges is necessary to correctly plan and distribute resources, especially given the current international climate of “deinstitutionalization." Israel, too, is implementing “reform” in the national psychiatric system – to transfer psychiatric treatment from a hospital to a community setting

Objectives: To analyze admission and discharge patterns, explore trends in psychiatric hospital length of stay, and compare these characteristics between first-episode and chronic patients, between children, youth and adults, and between hospitals.

Methods: All admissions and discharges from inpatient psychiatric wards between the years 2000 and 2004 were analyzed and characterized according to age, length of hospitalization, legal status, and nature of admitting institution (state hospital, health fund, general hospital).

Results: Mean length of stay in adults decreased during the 5 year study period, from 37.6 days in 2000 to 36.4 days in 2004. In years with higher admissions, hospital stay was shorter (P < 0.05). Length of stay in psychiatric wards in general hospitals was shorter than in state hospitals (P < 0.001). In contrast to adults and children, length of stay among adolescents showed a gradual increase (P < 0.05). Involuntary hospitalization comprised 25.3% of all admissions, and 16.8% of discharged patients were readmitted within 30 days. A dramatic decrease (24.3%) in the number of chronic hospitalizations was noted.

Conclusions: Various factors may account for these developments. Protracted hospitalizations may be reduced through changes in various aspects of treatment planning and psychiatric care continuum. The decrease in number of admissions, length of stay and number of chronically admitted patients remains in line with international practices. Particular attention needs to be devoted to planning and funding so that availability of community services matches reduction in psychiatric hospitalization.
 

M. Shani

In the last few decades there has been a tendency towards reinstitutionalization.

October 2005
O. Nissim, M. Bakon, B. Ben Zeev, E. Goshen, N. Knoller, M. Hadani and Z. Feldman.
 Moyamoya disease is a cerebral vasculopathy characterized mainly by progressive narrowing of the major intracranial vessels. While more common and having a familial predilection in the Far East, it can also develop in association with some common hereditary diseases and can be acquired after environmental exposure. In the young its manifestations are the result of cerebral ischemia. Adults usually suffer from repeated incidents of intracerebral hemorrhage. Surgical revascularization of ischemic cerebral territories plays a major role in their treatment. We review the literature and present our series of three adult and five pediatric patients; these patients were diagnosed at our institution and treated with indirect revascularization techniques.

 

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